CA2260674A1 - Method of predicting body composition in prepubertal children infected with human immunodeficiency virus - Google Patents

Method of predicting body composition in prepubertal children infected with human immunodeficiency virus Download PDF

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Publication number
CA2260674A1
CA2260674A1 CA002260674A CA2260674A CA2260674A1 CA 2260674 A1 CA2260674 A1 CA 2260674A1 CA 002260674 A CA002260674 A CA 002260674A CA 2260674 A CA2260674 A CA 2260674A CA 2260674 A1 CA2260674 A1 CA 2260674A1
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Prior art keywords
tbw
ffm
total body
child
height
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CA002260674A
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French (fr)
Inventor
Jack Wang
Mary Horlick
Donald P. Kotler
Richard N. Pierson
John Thornton
Stephen M. Arpadi
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ST LUKE'S-ROOSEVELT HOSPITAL
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Individual
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/05Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/053Measuring electrical impedance or conductance of a portion of the body
    • A61B5/0537Measuring body composition by impedance, e.g. tissue hydration or fat content
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/103Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/48Other medical applications
    • A61B5/4869Determining body composition
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/48Other medical applications
    • A61B5/4869Determining body composition
    • A61B5/4872Body fat

Abstract

A method for predicting fat free mass (FFM) and total body water (TBW) of a prepubertal child infected with human immunodeficiency virus (HIV) comprises the steps of measuring a child's height, measuring the child's total body resistance, and predicting fat free mass (FFM) and total body weight (TBW) of said child using the measured height and total body resistance.

Description

CA 0 2 2 6 0 6 7 4 I g 9 9 - o l - o ~

WO 98/~1216 PCT/US98/09712 -MF.THOD OF PREI~ICTING BODY COMPOSITION IN PRI~PUBERTAL
CHILDREN INFECTED WITH HUMAN IMMUI~ODEFICIENCY VIRUS

SPECIFICATION

BACKGROUND OF THE INVENTION
Growth failure and wasting are common complications of Hurnan Immunodeficiency Virus (HIV) infection in children, contributing to the morbidity and mortality. The ability to measure body composition gain or loss in these children associated with infection is crucial to clinical study in ways to alleviate these problems. Developing precise methods for measuring body composition in order to 10 monitor nutritional status in these children is an important area of research.
Traditional methods for determining body composition have limited availability and can be difficult to perform, especially with young children.
Bioimpedance analysis (BIA), on the other hand, is inexpensive, rapid and non-invasive. To perform body composition analysis, the bioimpedance analyzer 15 is affixed to a patient's wrist and ankle with electrodes. A current of approximately 800 microamps at 50 kHz is then delivered. Resi~t~n~e (the voltage drop of the applied current) and reactance (opposition to electric current caused by capitance) are then measured in a matter of minutes These values, along with other variables, are used to predict different body composition variables.
Due to its ease of use and portability, BIA has been demonstrated to be an attractive alternative to traditional methods for çstim~tin~ total body water (TBW) and fat free mass (FFM) in children. For instance, the following predictive equations have been developed for estimating TBW using BIA where H = height, R = resist~nce, W = weight and Z = impedance.
Fjeld et al. developed equations for predicting TBW in well and malnourished children as:
TBW = 0.48 + 0.68 (H21R), and CA 02260674 1999-01-0~

W O 98/51216 PCT~US98/09712 TBW = 0.76 + 0.18 (H2/R) + 0.39 ( W ). Fjeld et al., Total Body Water Measured by 0 Dilution and Bioelectric Impedance in Well and Malnourished Children, 27 Pediatric Research 98-02 (1990).
Danford et al. determined a predictive equation for TBW, using the tetrapolar method of BIA as:
TBW = 1.84 + 0.45 (H21R) + 0.11 (W). Danford et al., Comparison of Two Bioelectrical Impedance Analysis Models for Total Body Water Measurement in Children, 19 Annals of Human Biology 603-607 (1992).
Davies et al. found that TBW results using the following equation were 10 highly predictive:
TBW = -0.5 + 0.60 (H2/R). Davies et al., The Prediction of Total Body Water Using Bioelectric Impedance in Children and AdolescPntc, 15 Annals of Human Biology, 237-240 (1987).
Gregory et al. used the following equation to predict TBW in children lS with growth disorders:
TBW = 0.79 + O.S5 (H2/Z). Gregory et al., Body Water Measurement in Growth Disorders: A Comparison of Bioelectrical Impedance and Skinfold Thickness Techniques With Isotope Dilution, 66 Archives of Disease in Children 220-222 (1991) Davies and Gregory went on to find that combining their equations into one equation resulted in a more accurate predictor of TBW:
TBW = 0.13 + 0.58 (H2/Z). Davies and Gregory, Body Water Measurements in Growth Disorders, 66 Archives of Diseases in Childhood 1467 (1991).
The following predictive equations have been developed for estim~ting FFM. Deurenberg et al. found that several predictive equations were required to estimate FFM and that choice of the most accurate equation was dependent on the age of the children. Two of the equations are:
FF M = 0.640 (104) (H2/R) + 4.83, (Ages 7-9 for boys & girls) FFM = 0.488 (104) (H~R) + 0.221 (W) + 12.77 (H) - 14.7, (Ages 10-12 for girls and 10-lS for boys).

CA 02260674 1999-01-0~

98/51216 PCr/US98/09712 Deurenberg et al., ~ses~m~nt of Body Composition by Bioelectric Impedance in Children and Young Adults is Strongly Age-Dependent, 44 European Journal of Clinical Nutrition 261-268 (1989).
Cordain et al. evaluated BIA with children using the following equation to predict FFM:
FFM = 6.86 + 0.81 (H2/R). Cordain et al., Body Composition Determination in Children Using Bioelectrical Impedance, 52 Growth. Development & Aging 37 ~0 (1988).
Houtkooper et al. studied several predictive equations and recomrnended the following for predicting FFM:
FFM = -.61 (H2/R) + 0.25 (W) + 1.31. Houtkooper et al., Bioelectrical Impedance Fstim~tion of Fat-Free Body Mass in Children and Youth: A Cross-Validation Study, 72 J. Appl. Physiol. 366-73 (1992).
No studies, however, have ~sessed the accuracy of BIA, using standard equations, in predicting TBW and FFM in children infected with HIV.
An object of the present invention is to provide an improved method for predicting FFM and TBW in children infected with HIV which is more accurate than other known methods.
A further object of the invention is to provide a method for estim~ting FFM and TBW in these subjects which is clinically practical and more accommodating than other methods.
Further objects of the invention will readily appear to those skilled in the art from a review of the invention as disclosed and claimed.

SUMMARY OF THE INVF~TION
In accordance with the present invention, a method for predicting fat free mass (FFM) and total body water (TBW) of a prepubertal child infected with human immunodeficiency virus (HIV) is disclosed whereby total body resistance and height are measured to predict the body composition values.
Preferably. the total body resistance is determined by perforrning bioimpedance analysis (BIA) on a subject using the results to calculate resistance CA 02260674 1999-01-0~

Wo 98/51216 Pcr/uss8/097l2 according to previously derived fommulae known in the art. A tetrapolar bioimpedance analyzer is preferred.

DETATT.Fl) DESCRIPTION
A study using 20 subjects was performed to assess the perforrnance of bioimpedance analysis (BIA) in the prediction of total body water (TBW) and fat free mass (FFM) using standard equations in children infected with human immunodeficiency virus (HIV). The study suggests that TBW and FFM can be estim~ted in children with HIV using BIA with special equations specifically developed in this group of children.

Methods and Subjects The subjects were twenty prepubertal children ages 4-11 years with HIV infection as defined by the Centers for Disease Control and Prevention (CDC)criteria. They were recruited for the study from the St. Lukes-Roosevelt Hospital Center Pediatric HIV/AIDS Program.
The characteristics of the study subjects are p~esented in Table 1 below. Nineteen of the subjects acquired HIV as a result of perinatal tr~n~mi~sion and one was infected as a result of a blood transfusion while a neonate. Most of them had moderate to severe symptoms of HIV infection including moderate to severe immunodeficiency. None had known or suspected active secondary or opportunistic infections or clinically ~p~ ellt cardiac or renal disease.
After an ovemight fast, measurements were taken. The subjects were weighed to the nearest 0.01 kg using a beam balance. Their height was measured to the nearest 0.1 cm using a fixed wall-mounted stadiometer. Total body resistance (R) and reactance were measured with a tetra polar bioelectrical impedance analyzer m~nllf~rtured bv RJL Systems (RJL model 101 A, Detroit, MI) using bioimpedance analysis (BIA) techniques as disclosed in allowed U.S. Patent Application Serial No.
08/353,933 to Kotler, now pending, filed on December 12, 1994, which is incorporated herein by reference.

CA 02260674 lgg9-ol-o~

wo 98/51216 PCT/USg8/09712 .
s To assess the accuracy of the BIA, TBWwas independently measured by a dilution technique with an oral dose of 0.1 gm/lb of body weight of deuterium oxide with concentration of tracer measured in saliva (2H2O dilution). FFM was also ~.ce5se~1 by dual energy x-ray absorptiometry (DXA) using Lunar DPX and pediatric software, v. 8e. Growth and results of Iymphocyte phenotype analyses performed within 3 months of the study were obtained from each subject's medical records.
Eight published prediction equations, as disclosed above, for TBW and FFM in children, based on BIA, including two developed for children with growth disorders, which used simple, easily obtained measurements, were selected for the study. The values predicted by these prior art equations were compared to the measured values in the subjects of the present invention using the paired t test.
According to the present invention, new equations have been derived for TBW and FFM using regression techniques. The Box-Cox family of transformations was used to deterrnine if it was n eces.c~ y to transforrn the dependent variables and to identify the transformations. The set of independent variables considered for inclusion in the model included (height2/resist~n~e), (height2/reactance), weight and age. Residual analyses were perforrned on the final equations. The Epinfo (USD, Inc. Stone Mountain GA) software package was used for calculation of the height, weight and weight for height-age-percentiles. Allstatistical calculations were performed using the STATA (Computing Resource Center, Santa Monica~ CA) and SAS (SAS lnstitute, Inc., Cary, NC) software packages for personal computers. The level of significance for all statistical tests was 0.05.

Results Table 2 presents results of the comparison of TBW and FFM predicted from the published equations referenced above with TBW measured by2H,O dilution and FFM measured by DXA. The values predicted by each equation were signif:cantly different from those measured (correlation coefficient (p) values ranging from 0.02 to 0.001).

CA 02260674 1999-01-0~

~0 98151216 PCT/US98/09712 Since none of the tested published equations adequately predicted TBW or FFM in the sample group of the present invention, two regression equations according to the present invention were developed for this sample as follows:
Log(TBW) = 1.65 + 0.05 (H2/R) (r2=.95, SEE=0.068) and FFM = 1.34 + 0.70 (A) + 0.68 (H2/R) (r2=.95, SEE=1.23);
where:
TBW = total body water (l) FFM = fat free mass (kg) H = height (cm);
10 A = age (yrs);
R = reci~t~nce (ohms);
r = correlation coefficient; and SEE = standard error estim~te~
The addition of sex, weight and (height2/re~ct~re.) did not significantly improve the 15 prediction of either TBW or FFM in the study.

Discussion These results indicate that the published standard equations established for generally predicting body composition from BlA-derived measurements in children are not valid for application to children with HIV infection. This study also 20 indicates that highly predictive equations specific for this population using simple, standard variables can be devised. lndeed, predictive equations based on BIA-derived resistance which provide estimates of TBW and FFM comparable to those of traditional, more complex methods of body composition measurements were derived in the present invention. As a result, the new equations of the present invention 25 provide a means for using BIA to predict body coll~pdrLIl~ents (TBW or FFM) in children with moderate to severe symptoms of HIV, moderate to severe immunodeficiency, and with abnormal growth, such as those included in the study.While the foregoing indicates the preferred embodiments of the invention claimed below~ those skilled in the art will appreciate that there arevariations of this disclosure which do not depart from the scope of the invention -claimed herein. For example, dirr~,le.~ methods of BIA may be used in conjunction with the claimed equations such as those providing different amperages and frequencies.

Table 1. Characteristics of 20 HIV-infected children undergoing study.

Variable Mean + SD (range) Age (yrs) 6.5 + 2.3 (4-11) Height (cm) 117.4 + 13.8 (97.9-147.5) Height-for-age-percentile (%) 35.2 + 29.8 (0.1 -93.1) Weight (kg) 23.3 + 7.9 (14.1-44.5) Weight-for-age-percentile (%) 43.4 + 36.6 (2.5-96.5) Weight-for-height percentile (%) 56.2 + 36.4 (2.8- 99.9) Total body water (L)a 13.7 + 4.6 (8.0-25.7) Fat free mass (kg~b 18.4 + 5.5 (11.6-31.0) Resict~nce (ohrns) 785 + 116(543-1012) Height2/Resistance 18.38 + 5.94 CD4 count (no/dl) 319 + 330 (4-1099) CD4 percent (%) 16.8 + 13.8 (0.6-40.4) No. (%) Race/ethnicity Black 6 (30) Hispanic 14 (70) CDC classification N3 1 (5) A2 3 (15) B2 3 (15) B3 5 (25) Cl 2 (10) C2 3 (15) C3 3 (15) , Growth pattern AIDS Wasting Syndrome' 2 (10) Progressive stuntingd 9 (45) Normal 9 (45) 5 Sex males g (45) females 11 (55) a Total Body water detçnnined by deuterium oxide dilution.
b Fat free mass determined by dual energy absorptiometry.
c Weight loss of > 10% within 3 months of study.
d Decline in height-for-age-percentile of 2 or more SD (e.g. 95th, 75th, 50th, 25th, 5th percentile for age) within 2 years before, or 6 months after the time of study and without weight loss.

, . . . . .

WO 9815~216 PCr/US98/09712 Table 2. Evaluation of BIA-based predictive equations for TBW and FFM with TBW
me~u,~d by deuterium oxide dilution and FFM by dual X-ray absorptiometry in children infected with H~V.

Prcdictcd Prcdicted-~ody WcightMcasurcd:
Studv NA~e ~yrs~ Variables Cl , (+SD) (k~)' p Fjeld et al. 30 0.4-3H2/R,W TBW 12.95 .75 .02 (4.1) Danford et al. 37 5-9 H2/R,W TBW 12.81 .88 .009 (3.94) Daviesetal. 26 5-18 H2/R TBW10.61 3.03 .001 (3.64) Gregory et al. 34 7-15 H2/R TBW 11.03 -2.67 .001 (3.3) Davies and 60 5-18 H2/R TBW10.93 -2.77 .001 1 0 Gre~ory (3.5) De.~ et 8277-25 H2/R,G,A,W,H FFM16.08 -2.28 .001 al. (4.88) Cordain et al. 30 9-14 H2/RFFM 21.75 3.39 .001 (4.82) I!ou~ oper et 94 10-14 H2/R,W,X~ FFM 19.69 1.33 .001 15 al. (4.93) ' Values ex~ ssed as mean + SD.

' TBW measured by deuterium oxide dilution (mean = 13.7 L) and FFM measured by dual X-ray absorptiometry (mean = 18.4 kg), as presented in Table 1.
20 TBW = total body water FFM = fat free mass H = height W = weight R = resi~t~noe 25 A=age WO 98/51216 PCI'/US98/09712 G = gender Xc = RPs~rt~nre N = number subjects studied p = cGl~l~ion coefficient

Claims (6)

1. A method for predicting fat free mass (FFM) and total body water (IBW) of a prepubertal child infected with human immunodeficiency virus (HIV), comprising the steps of:
measuring a height of said child;
measuring total body resistance of said child; and predicting fat free mass (FFM) and total body weight (TBW) of said child using said height and said total body resistance.
2. A method for predicting fat free mass (FFM) and total body water (TBW) of a prepubertal child infected with human immunodeficiency virus (HIV), comprising the steps of:
measuring a height of said child;
providing at least one signal representative of said height;
measuring total body resistance of said child;
providing at least one signal representative of said resistance;
and predicting fat free mass (FFM) and total body weight (TBW) of said child using said signals.
3. The method of claim 2 wherein said resistance measuring step comprises the step of using a bioimpedance analyzer.
4. The method of claim 3 wherein the bioimpedance analyzer is a tetrapolar bioimpedance analyzer.
5. The method of claim 1 wherein the predicting step comprises the steps of determining fat free mass and total body water of said child, according to:
FFM = 1.34 + 0.70 A + 0.68 H2/R and Log (TBW) = 1.65 + 0.05 H2/R
where:

FFM = fat free mass (kg) TBW = total body water (1) A = age (yrs) H = height (cm) and R = total body resistance (ohms).
6. The method of claim 2 wherein the predicting step comprises the steps of determining fat free mass and total body water of said child, according to:
FFM= 1.34 + 0.70 A + 0.68 H2/R and Log (TBW) = 1.65 + 0.05 H2/R
where:
FFM = fat free mass (kg) TBW = total body water (1) A = age (yrs) H = height (cm) and R = total body resistance (ohms).
CA002260674A 1997-05-16 1998-05-13 Method of predicting body composition in prepubertal children infected with human immunodeficiency virus Abandoned CA2260674A1 (en)

Applications Claiming Priority (2)

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US08/857,390 1997-05-16

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US6280396B1 (en) * 1998-08-03 2001-08-28 American Weights And Measures Apparatus and method for measuring body composition
DE20116409U1 (en) 2000-09-30 2002-01-24 Fook Tin Plastic Factory Ltd Body fat measuring device
US6477409B2 (en) * 2000-10-04 2002-11-05 Tanita Corporation Apparatus for measuring basal metabolism
US20070202565A1 (en) * 2006-02-27 2007-08-30 Fleury Debra J Growth plotter

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US5086781A (en) * 1989-11-14 1992-02-11 Bookspan Mark A Bioelectric apparatus for monitoring body fluid compartments
US5126324A (en) * 1990-06-07 1992-06-30 Genentech, Inc. Method of enhancing growth in patients using combination therapy
KR0123408B1 (en) * 1994-09-15 1997-11-11 차기철 Method and apparatus for determining body composition using bioelectrical impedance analysis
US5615689A (en) * 1994-12-12 1997-04-01 St. Luke's-Roosevelt Hospital Method of predicting body cell mass using bioimpedance analysis
US5628328A (en) * 1995-04-25 1997-05-13 Iowa State University Research Foundation Method for measuring muscle mass
KR0161602B1 (en) * 1995-06-24 1999-01-15 이재석 Component analysis of human body and analytical method thereof using bioelectrical impedance analysis

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BR9804903A (en) 2000-01-25
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CA2260674A1 (en) Method of predicting body composition in prepubertal children infected with human immunodeficiency virus

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